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Superselective microcoil embolization for the treatment of lower gastrointestinal hemorrhage.

PURPOSE: To evaluate the safety and effectiveness of superselective microcoil embolization for the treatment of lower gastrointestinal (LGI) hemorrhage. MATERIALS AND METHODS: A retrospective review of LGI superselective microcoil embolization data for a 10-year period was performed. During this period, twenty-two patients with evidence on angiography of LGI bleeding underwent superselective microcoil embolization. Hemorrhage was treated in the colon (n = 19) and jejunum (n = 3). Ivalon was used adjunctively in two patients and gelfoam was used as a secondary agent in two additional patients. Postembolization ischemia was evaluated objectively in 14 patients by colonoscopy (n = 10), surgical specimen (n = 3), and barium enema (n = 1). All patients were followed for clinical evidence of bowel ischemia. Four patients died before further follow-up could be performed. Additionally, 122 cases of LGI hemorrhage treated with superselective microcoil embolization were identified in a review of the literature. A meta-analysis was then performed, combining the data in this study and the data from the literature, to estimate the rate of major and minor ischemic complications on a total of 144 superselective microcoil embolizations. RESULTS: Immediate hemostasis was achieved in all 22 patients in this study. Complete clinical success was achieved in 86% of patients (19 of 22 patients). Rebleeding occurred in 14% of patients (3 of 22 patients) and each underwent colonoscopic intervention with success. Postembolization objective follow-up was performed in 64% of patients (14 of 22 patients). Ten patients underwent follow-up colonoscopy; one patient received a follow-up barium enema; and three patients underwent subsequent surgery. Colonic resection (one partial and one total) was performed in two patients. The partial colectomy was performed in a patient who had been diagnosed with colonic polyps and dysplasia. The total colectomy was performed on a patient with history of chronic LGI bleeding complicated by long-term anticoagulation therapy and a history of tubular adenoma resection. The third surgical patient (16 months old) underwent a follow-up exploratory laparotomy after embolization of a proximal jejunal branch of the superior mesenteric artery. None of the three patients who underwent surgery were found to have postembolic ischemic changes in the bowel specimen. Four patients in this study died, for reasons unrelated to hemorrhage or embolization, before further follow-up could be performed. The last four patients were followed clinically and experienced no symptoms of intestinal ischemia. A minor ischemic complication was reported in 4.5% of patients (1 of 22 patients), and there were no major ischemic complications (0%) in this series. A review of the data from 122 cases of LGI superselective microcoil embolization in the literature is also presented. Combined with the data in this study, the minor complication rate was 9% (13 of 144 patients), and the major complication rate was 0% (0 of 144 patients). CONCLUSION: Superselective microcoil embolization is a safe and effective treatment for LGI hemorrhage.

Adolescent↗

Effect of alpha-difluoromethylornithine on rectal mucosal levels of polyamines in a randomized, double-blinded trial for colon cancer prevention.

BACKGROUND: Polyamines (e.g., putrescine, spermidine, and spermine) are required for optimal cell growth. Inhibition of polyamine synthesis suppresses carcinogen-induced epithelial cancers, including colon cancer, in animal models. In a short-term phase IIa trial, we determined that low doses of alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (an enzyme involved in polyamine synthesis), reduced the polyamine content of normal-appearing rectal mucosa of subjects with a prior history of resected colon polyps. In a follow-up study, we have attempted to determine the lowest dose of DFMO that can suppress the polyamine content of rectal mucosa over a course of 1 year with no or minimal side effects. METHODS: Participants were randomly assigned to daily oral treatment with a placebo or one of three doses (0.075, 0.20, or 0.40 g/m2) of DFMO. Baseline and serial determinations of polyamine levels in rectal mucosa and extensive symptom monitoring (including audiometric measurements, since DFMO causes some reversible hearing loss at higher doses) were performed over a 15-month period. RESULTS: DFMO treatment reduced putrescine levels in a dose-dependent manner. Following 6 months of treatment, doses of 0.20 and 0.40 g/m2 per day reduced putrescine levels to approximately 34% and 10%, respectively, of those observed in the placebo group. Smaller decreases were seen in spermidine levels and spermidine:spermine ratios. Polyamine levels increased toward baseline values after discontinuation of DFMO. Although there were no statistically significant differences among the dose groups with respect to clinically important shifts in audiometric thresholds and nonaudiologic side effects, statistically significant higher dropout and discontinuation rates were observed in the highest dose group. CONCLUSIONS: Polyamine levels in rectal mucosa can be continuously suppressed by daily oral doses of DFMO that produce few or no side effects. A dose of 0.20 g/m2 can be used safely in combination phase IIb or single-agent phase III chemoprevention trials.

Adult↗

Selenium, copper, and zinc concentrations in intestinal cancer tissue and in colon and rectum polyps.

The prospective randomized trial was used to determine Se, Zn, and Cu concentrations in intestinal cancer tissue and colorectal polyp. We also determined the relationship among the trace element levels in cancer tissue, the localization of neoplasms, and the stage of their development. The concentrations of these trace elements were examined in cancer tissue of the colorectum in 67 patients and in the colon and rectum polyps in 42 patients using the total-reflection X-ray fluorescence (TRXRF) method. The mean concentration of Se in colorectal cancer was 0.86 microg/g tissue and was statistically higher than in the case of polyps (0.57 microg/g). The mean concentration of Zn in colorectal cancer was higher than in the polyp (14.8 microg/g and 9.84 microg/g, respectively). The determined average concentration of Cu in colorectal cancer was 3.87 microg/g tissue and was a little lower than the level of this metal in the polyp (3.94 microg/g). There was no difference in the levels of these trace elements depending on the location of the neoplasm and the stage of its development. Also, there was no difference between the concentrations of these trace elements in the cancer tissue of malignant and benign tumors after taking into consideration the sex and age of patients. During the examination, we determined significantly higher concentrations of only selenium and zinc in the cancer tissue and not in the polyp. The level of copper was lower in a malignant tumor than in a benign one.

Adult↗

Birt-Hogg-Dubé syndrome: a novel marker of kidney neoplasia.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is a dominantly inherited predisposition for development of fibrofolliculomas, trichodiscomas, and acrochordons. Concurrent internal tumors, such as colonic polyps and renal carcinoma, have been described in patients with BHD. OBJECTIVE: To evaluate kindreds with familial renal tumors for cutaneous manifestations of BHD. DESIGN: One hundred fifty-two patients from 49 families underwent complete oral and skin examination. Skin lesions were identified by their clinical appearance, and the diagnosis was confirmed by results of histologic examination. Individuals underwent screening for familial renal neoplasms. SETTING: A tertiary referral research hospital. PATIENTS: Individuals with familial renal tumors and their asymptomatic at-risk relatives. MAIN OUTCOME MEASURE: We determined whether any form of renal cancer is associated BHD. RESULTS: We identified 3 extended kindreds in whom renal neoplasms and BHD appeared to segregate together. Two kindreds had renal oncocytomas and a third had a variant of papillary renal cell carcinoma. Thirteen patients exhibited BHD. Seven individuals, including a set of identical twins, had renal neoplasms and BHD. An additional 4 patients (3 deceased and not examined) in these families had renal neoplasms but not BHD. Birt-Hogg-Dubé syndrome without renal neoplasms was present in 6 individuals. Thirteen patients with fibrofolliculomas and trichodiscomas presented clinically with multiple smooth skin-colored to grayish-white papules located on the face, auricles, neck, and upper trunk. Oral papules were present in 9 of 28 and achrochordons in 11 of 28 patients. Features of BHD not previously appreciated included deforming lipomas in 5, collagenomas in 4, and pulmonary cysts in 4 of 28 patients. Families with BHD did not display germline mutations in the von Hippel-Lindau gene or in the tyrosine kinase domain of the MET proto-oncogene. CONCLUSIONS: Birt-Hogg-Dubé syndrome may be associated with familial renal tumors. Birt-Hogg-Dubé and renal tumors segregate together in an autosomal dominant fashion. Patients with BHD and their relatives are at risk for development of renal tumors. Therefore, patients with BHD and their relatives should undergo abdominal computed tomography and renal ultrasound screening for renal tumors.

Adult↗

Transient bacteremia associated with barium enema.

A group of 175 patients had barium enema. Pour-plate blood cultures were obtained immediately before and after the procedure and 5, 10, 15, and 30 minutes later. Bacteremia was demonstrable in 20 (11.4%) patients. In some, blood cultures were positive for as long as 15 minutes after barium enema; all were negative at 30 minutes. Among the bacteria associated with the 20 episodes of bacteremia were Escherichia coli, Klebsiella, enterococci, Proteus morganii, Bacteroides, and Veillonella. The incidence of bacteremia among patients with ulcerative colitis, regional enteritis, rectal polyps, colonic or rectal carcinoma, nonspecific diarrhea, or other lower intestinal tract disorders was not much different from patients free of rectosigmoid disease. The results of this study suggest that a history of recent barium enema may be important in patients who have endocarditis.

Barium Sulfate↗

A second look at colonoscopy: indications, failures, and costs.

Results of colonoscopy and colonoscopic polypectomy in 599 patients have been reviewed. Added experience has not decreased the number of failures--failure to examine the entire colon, polyps not retrieved for histological examination ("lost polyps"), undetected ("missed") lesions, and false-negative biopsy specimens. The incidence of invasive carcinoma in polyps measuring under 1 cm is less than 1%; polypectomy should be reserved for larger lesions or demonstrated growth of small polyps. Diagnostic colonoscopy in selected patients (those with persistent gross or occult rectal bleeding but normal results from sigmoidoscopic and barium enema studies) demonstrates a causative lesion in greater than 25% and detects a cancer in 5% to 10% of patients.

Biopsy↗

Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial.

CONTEXT: Basic research and observational evidence as well as results from trials of colon polyp recurrence suggest a role for aspirin in the chemoprevention of cancer. OBJECTIVE: To examine the effect of aspirin on the risk of cancer among healthy women. DESIGN, SETTING, AND PARTICIPANTS: In the Women's Health Study, a randomized 2 x 2 factorial trial of aspirin and vitamin E conducted between September 1992 and March 2004, 39 876 US women aged at least 45 years and initially without previous history of cancer, cardiovascular disease, or other major chronic illness were randomly assigned to receive either aspirin or aspirin placebo and followed up for an average of 10.1 years. INTERVENTION: A dose of 100 mg of aspirin (n=19 934) or aspirin placebo (n=19 942) administered every other day. MAIN OUTCOME MEASURES: Confirmed newly diagnosed invasive cancer at any site, except for nonmelanoma skin cancer. Incidence of breast, colorectal, and lung cancer were secondary end points. RESULTS: No effect of aspirin was observed on total cancer (n = 2865; relative risk [RR], 1.01; 95% confidence interval [CI], 0.94-1.08; P = .87), breast cancer (n = 1230; RR, 0.98; 95% CI, 0.87-1.09; P = .68), colorectal cancer (n = 269; RR, 0.97; 95% CI, 0.77-1.24; P = .83), or cancer of any other site, with the exception of lung cancer for which there was a trend toward reduction in risk (n = 205; RR, 0.78; 95% CI, 0.59-1.03; P = .08). There was also no reduction in cancer mortality either overall (n = 583; RR, 0.95; 95% CI, 0.81-1.11; P = .51) or by site, except for lung cancer mortality (n = 140; RR, 0.70; 95% CI, 0.50-0.99; P = .04). No evidence of differential effects of aspirin by follow-up time or interaction with vitamin E was found. CONCLUSIONS: Results from this large-scale, long-term trial suggest that alternate day use of low-dose aspirin (100 mg) for an average 10 years of treatment does not lower risk of total, breast, colorectal, or other site-specific cancers. A protective effect on lung cancer or a benefit of higher doses of aspirin cannot be ruled out.

Aspirin↗

Spectrum of malignancy and premalignancy in Carney syndrome.

Carney syndrome is a rare, autosomal dominant, multi-system disorder comprising 8 well-characterized findings, only 2 of which need be present for a definitive diagnosis. Benign neoplasms are frequent, but malignancies are thought to be uncommon. We have studied a family to clarify the diagnosis and spectrum of clinical manifestations of the syndrome and to develop guidelines for management. The proposita, a 34-year-old woman had classic findings of Carney syndrome, invasive follicular carcinoma of the thyroid gland, Barrett metaplasia of the esophagus, neoplastic colonic polyps, bipolar affective disorder, and atypical mesenchymal neoplasm of the uterine cervix distinct from the myxoid uterine leiomyoma usually seen in this syndrome. Although thyroid gland neoplasm is rare in Carney syndrome, this patient's most aggressive manifestation was her thyroid carcinoma. The diagnosis of Carney syndrome was established in her 9-year-old son and is a probable diagnosis in her 12-year-old daughter. Endocrine manifestations were prominent in the family with at least 9 relatives in 3 generations affected with various endocrine abnormalities. The findings in this family indicate that the spectrum of manifestations in this pleiotropic gene apparently includes a malignant course with premalignant and endocrinologic disorders not previously recognized.

Adult↗

Familial glioblastoma with hepatic focal nodular hyperplasia.

Two siblings succumbed to glioblastoma multiforme, associated with hepatic focal nodular hyperplasia and cafe-au-lait spots. One sibling had syndactyly and multiple colonic polyps, while the other had an angiomatous malformation in the brain. Their mother died of myasthenia gravis. The findings suggest a hamartomatous syndrome of malformations that predisposes to brain tumors.

Adolescent↗

Increased tetraploidy: cell-specific for the Gardner gene in the cultured cell.

Human hereditary tumors in vivo are known to show tissue specificity. Increased endoreduplication with tetraploidy has been shown to occur in cultures established only from tissue containing epithelium (skin and colonic polyps) from patients with the Gardner syndrome. Cultures established from blood (short-term lymphocyte and lymphoid suspension) and connective tissue (subcutaneous tissue, lipoma, mesentery, and sebaceous cyst) from the same patients did not show increased tetraploidy. These observations demonstrated that tetraploidy as an expression of the gene for the Gardner syndrome was cell-specific in vitro and added further evidence that increased tetraploidy could be used for detection of the Gardner gene in families at risk.

Cell Line↗

Cronkhite-Canada syndrome. Case report.

The case report of a 72-year-old man with the characteristic clinical and pathologic-anatomic picture of the Cronkhite-Canada syndrome is presented. The clinical features and the radiographic appearance of the gastrointestinal tract suggested Ménétrier's disease. Subtotal gastrectomy was performed and at the subsequent pathologic-anatomic examination, the diagnosis of Cronkhite-Canada syndrome was made. The patient slowly recovered over the following five months while being treated with the so-called astronaut diet (Vivasorb) supplemented with vitamins, iron and electrolytes. He died five months after surgery from intercurrent disease. The differential diagnosis of gastrointestinal polyposis with or without mucocutaneous pigmentation is briefly discussed. The histochemical characteristics of the epithelium in the gastric and colonic polyps was studied in some detail. The authors believe that the gastrointestinal polyps in the Cronkhite-Canada syndrome are regenerative and non-neoplastic in nature.

Aged↗

Carcinoembryonic antigen (CEA) levels in benign gastrointestinal disease states.

Elevated circulating CEA levels occur in patients with benign gastrointestinal and hepatic disorders. These are usually less than 10 ng/ml. Of clinical importance is the influence of liver disease on the interpretation of CEA. At least 50% of patients with severe benign hepatic disease have elevated CEA levels, most often active alcoholic cirrhosis, and also chronic active and viral hepatitis, and cryptogenic and biliary cirrhosis. Patients with benign extrahepatic biliary obstruction may have increased plasma CEA, the highest in patients with co-existent cholangitis and especially liver abscess. The liver appears to be essential for the metabolism and/or excretion of CEA. Hence, liver work-up is needed to assess any patient with an elevated CEA. A damaged liver may further augment elevated CEA levels due to cancer. The increased circulating CEA observed in some patients with active ulcerative colitis tends to correlate with severity and extent of disease and usually returns to normal with remission. CEA levels also may be mildly elevated in patients with pancreatitis and in adults with colonic polyps. Smoking may contribute to the increased CEA levels seen in patients with alcoholic liver disease and pancreatitis. Therefore, in interpreting mildy elevated circulating CEA levels in patients with GI tract diseases, one must consider benign as well as malignant etiologies.

Animals↗

Familial T-cell lymphoblastic lymphoma: association with Von Recklinghausen neurofibromatosis and Gardner syndrome.

A family is described in which three of seven siblings developed a T-cell lymphoblastic lymphoma. Tumor cells formed rosettes with sheep erythrocytes, lacked surface Ig, and expressed human T- but not B-lymphocyte antigens. They lacked the enzyme terminal transferase suggesting a lymph node rather than thymic T-cell origin. Autopsy findings supported this conclusion. All three sibs, like their father, had numerous cafe'-au'lait spots indicative of Von Recklinghausen neurofibromatosis. One child had a subcutaneous fibroma, and another had multiple colonic polyps and exostoses characteristic of Gardner syndrome. Both are autosomal dominant conditions known to predispose to malignancies. The genetic factors responsible for these conditions may also predispose to the development of "post-thymic" T-cell lymphoblastic lymphoma.

Child↗

Association of congenital hypertrophy of the retinal pigment epithelium with familial adenomatous polyposis.

Ophthalmological examinations were performed in 49 people (43 patients) from 24 families affected by familial adenomatous polyposis (FAP). No features of congenital hypertrophy of the retinal pigmented epithelium (CHRPE) were noted in six first-degree relatives without colonic polyps. Patients with Gardner's syndrome exhibited CHRPE more frequently than those without exostosis or desmoid tumour (91 per cent versus 45 per cent). In addition the prevalence of CHRPE was slightly higher in the patients with gastric or duodenal polyps (68 per cent compared with 50 per cent) in those who had a normal gastroduodenal examination. There were 11 families in which two or more patients underwent ophthalmological examinations. In five of these 11 families, all 12 patients were negative for CHRPE. In four of the remaining six families, all 11 patients had CHRPE. CHRPE is one of the pleiotropy of FAP and ophthalmological examination is an important screening test for the family of patients with CHRPE associated with FAP.

Adenomatous Polyposis Coli↗

An improved snare system for the nonsurgical retrieval of intravascular foreign bodies.

We have modified a snare technique originally described for transcolonoscopic removal of colonic polyps for the retrieval of intravascular foreign bodies. The key difference from other snare techniques is the employment of a wire snare with a crimp in its midportion that enables the formation of a loop in a plane perpendicular to the axial direction of the guiding catheter. With this technique we have quickly removed a variety of objects from the right heart and pulmonary arteries in four patients.

Blood Vessels↗